I plan to study the generality of DNA error-corrective mechanisms in terms of (1) the repair of different types of damage relevant to cellular pathology; and (2) regulation of repair reactions with respect to normal physiological reactions such as replication, transcription, and recombination. This work will involve: (1) studying the effect of certain types of damage (e.g., UV in DNA) on in vitro DNA synthesis, transcription, and in enzyme reactions which catalyze one or more repair steps; (2) study of the rate determining steps in the repair of viral and prokaryotic DNA in vivo, and their influence on subsequent DNA replication, recombination, and transcription. Studies of this kind serve a two-fold purpose. First, they extend our knowledge about the basic properties of DNA, how the need for maintaining structural integrity is balanced with the evolutionary requirement for genetic plasticity, and the manner in which enzymes involved in DNA metabolism regulate their activity. Second, they serve the more practical end in attempting to explain certain pathological processes in terms of underlying changes at the molecular level. Faulty repair has already been implicated in certain skin cancers, and could serve as a useful approach to study other sunlight induced dermatological conditions, as well as other neoplastic changes. BIBLIOGRAPHIC REFERENCES: Patrick, M. H. "Physical Chemical Properties of DNA" in Photochemistry and Photobiology of Nucleic Acids (ed. S. Y. Wang), Vol. II, Chap. 1. Academic Press, N. Y. (1976). Patrick, M. H. "Substrate Specificity of a UV endonuclease from M. luteus", in Molecular Mechanisms for the Repair of DNA: Part A (ed. P. Hanawalt and R. Setlow), Plenum Press (1975).